|Year : 2021 | Volume
| Issue : 4 | Page : 301-305
Revisiting pediatric alopecia areata: Newer insights
Yashpal Manchanda1, Ramkumar Ramamoorthy2
1 Department of Dermatology, Farwaniya Hospital, Farwaniya, Kuwait
2 Department of Pediatric Dermatology, Kanchi Kamakoti Childs Trust Hospital, Chennai, Tamil Nadu, India
|Date of Submission||13-Apr-2021|
|Date of Decision||21-Jul-2021|
|Date of Acceptance||04-Sep-2021|
|Date of Web Publication||01-Oct-2021|
P. O. Box 2372, Ardiya 92400
Source of Support: None, Conflict of Interest: None
Alopecia areata (AA) is an autoimmune disorder that results from the targeted attack of hair follicles by multiple T-cell subsets leading to hair loss. Childhood-onset AA is characterized by a severe clinical course with a poorer treatment outcome. However, it does carry a significant detrimental impact on the quality of life and the self-confidence of the child, besides impairing the emotional health of parents in severely affected cases. The data on pediatric AA is limited. Despite numerous advances made in recent years for the management of AA in children, Food and Drug Administration approved systemic treatment required for severe AA cases is still elusive. In this review, we review the recent literature on clinical manifestations, comorbidities, investigations, and the treatment modalities of AA in children.
Keywords: Alopecia areata, newer insights, pediatric
|How to cite this article:|
Manchanda Y, Ramamoorthy R. Revisiting pediatric alopecia areata: Newer insights. Indian J Paediatr Dermatol 2021;22:301-5
|How to cite this URL:|
Manchanda Y, Ramamoorthy R. Revisiting pediatric alopecia areata: Newer insights. Indian J Paediatr Dermatol [serial online] 2021 [cited 2021 Dec 5];22:301-5. Available from: https://www.ijpd.in/text.asp?2021/22/4/301/327441
| Introduction|| |
The various facets in the diagnosis and treatment of childhood alopecia areata (AA) had been the subject matter of a previous publication in this journal in the year 2017. This article is an attempt to focus on the recent highlights in pediatric AA.
| Epidemiology|| |
AA in the Childhood or pediatric age group is a very commonly diagnosed condition, with more than half of the total cases diagnosed with AA reporting to have developed the first episode at <20 years of age. Recent meta-analysis has pegged the prevalence rate of pediatric AA at 1.92%. It is estimated that pediatric AA accounts for 18.1% of all AA patients.
| Pathogenesis|| |
AA is an autoimmune disorder mediated by inflammatory cells attacking the hair bulb secondary to loss of the immune privilege of the anagen hair follicle. However, the initial event inducing the collapse of immune privilege may be autoimmune or nonautoimmune (stress, dysbiosis, free radical injury).
Recent observations have thrown light on the complex immune profile of AA. A multi-cytokine signature due to both local and systemic activation of Th1, Th2, Th9, and Th17 cells is revealed by these studies. Psychiatric comorbidities commonly associated with AA such as anxiety and depression could be mediated by cytokines IL6, IL1beta, and IL 17, which belong to the Th17 axis. Immunoglobulin E (IgE) levels and Th2 cytokines are elevated in AA irrespective of the presence of atopy. Atopic dermatitis (AD) is more commonly seen in association with severe AA than in patchy AA and is a marker of poor response to treatment for AA. Chronicity of AA was linked to the Th1 cytokine IF Gamma, whereas severity was correlated with the intensity of activation Th2 pathway in skin and blood. Th2 cytokines were not elevated in localized AA, as reported in a recently published Indian study.
The peribulbar inflammatory infiltrate is composed of CD4 cells, CD8+ NKG2D+ T cell, and NK cells. These CD8+ NKG2D+ T cells, in turn, produce Interferon-gamma (IFNγ), that binds to its receptors present on the surface of the hair follicle epithelial cells thus activating the JAK1/2– STAT1 pathway, leading to the promotion of IL15 production. IL15 binds its receptor on the surface of the T-cells and activates the JAK1/3 – STAT5 pathway which promotes the production of IFNγ perpetuating the loop. The inhibition of the JAK-STAT pathway using JAK inhibitors leads to interruption of the intracellular signaling and ultimately blocks the T cell-mediated peribulbar inflammation. According to a recent report, JAK 3 plays a more important role in the immunopathogenesis of AA than JAK 1. The success of JAK inhibitors has opened new avenues for the exploration of strategies based on the immunopathogenesis of AA.
| Comorbidities and screening recommendations|| |
Childhood-onset AA has been associated with a different profile of comorbidities compared to adult-onset AA. AD is most common in children younger than 10 years of age. while thyroid disorders are more frequently found in patients who had developed AA after 60 years of age. AD is the most frequent comorbidity reported in Pediatric AA. Concomitant presence of atopy, particularly AD is a marker of poor prognosis. A study done on 3510 children diagnosed with AA, the majority of whom were in the age group 10-18 showed an association of metabolic disorders such as obesity, hyperlipidemia, and diabetes with AA in addition to autoimmune conditions. A high prevalence of asymptomatic CD in childhood AA has been reported in a recent study. However autoimmune comorbidities are less commonly reported in children compared to the adult population. Routine testing for thyroid functions is not required in childhood AA. In the absence of goiter and/or suggestive features of hypothyroidism or family history of thyroid disease, thyroid screening with Free T4, and TSH is required only in children with Down syndrome or personal history of atopy. Other significant group of associated morbidities being increasingly recognized in recent times are psychosocial comorbidities. AA in children and adolescents (aged 7-19 years) were related to the occurrence of stressful life events before disease onset. AA has a significant negative impact on the quality of life and self-confidence of the child, and in some extreme cases could even be a reason for committing suicide in children. Furthermore, to note is the fact that some of these comorbidities can be either induced or at least worsened because of the drugs used to treat AA.
| Prognosis|| |
Childhood onset of AA is one among the various factors that [Table 1] predict a poorer prognosis.,,
Although, approximately half of the patients are likely to experience spontaneous regrowth within a year of diagnosis, about 5% of AA cases will eventually progress to severe forms (AT and AU). In general, AA follows a prolonged course punctuated with periods of recurrences and remissions.
| Investigations|| |
Dermoscopy has recently emerged as a vital investigative tool for assisting the diagnosis of AA. It is also useful for assessing the severity of the disease and monitoring the response to treatment. Although yellow dots and vellus hairs are considered as the most sensitive markers for AA, yellow dots are less commonly seen in the pediatric population due to the underdevelopment of sebaceous glands in prepubertal children. Short vellus hairs and empty follicular openings are the commonest findings in children.
| Treatment|| |
A wide range of therapeutic options have been used to treat AA in children. It is difficult to evaluate the efficacy of any therapeutic intervention in view of the highly unpredictable nature of the disease and the high rate of spontaneous remission.
| Topical Agents|| |
Potent or super potent class of topical steroids are the first choice of treatment in cases of pediatric AA. According to a recently published metanalysis, the level of evidence regarding their efficacy is fairly good (level II according to The Oxford 2011 Levels of Evidence), in the sense that there are the number of observational studies in its support. It reported 81% response rate, but showed that more than half of the patients had relapsed on stoppage of therapy. Topical steroids must be used for 2-3 months after improvement in hair growth and gradually tapered. Washing the head or the applied area 12 h after application may reduce the incidence of scalp folliculitis in children. Intralesional steroid injections are poorly tolerated due to fear of pain and are generally not used, except in some older children or adolescents with localized lesions.
The two most popularly used topical contact sensitizing agents are diphencyclopropenone (DPCP) and squaric acid dibutyl ester (SADBE) (highest level of evidence: III). In a cohort of 108 children aged 4–18 years, diagnosed with long-standing AA recalcitrant to topical therapeutic options, immunotherapy with DPCP showed significant results in 30% with complete growth in 10% of children. The results were not related to disease extent and the presence of concomitant atopy. However, three-fourths of children experienced adverse events such as dermatitis, urticaria, and regional lymphadenopathy. The response rate was 54.5% in a study done on Indian patients aged 6–51 years. The incidence of adverse effects following topical immunotherapy was correlated to the pretreatment levels of IgE. The levels of Th2 cell-derived cytokines were increased following treatment with DPCP, underscoring the need for a cautious approach in children who have AA with concomitant AD. The risk of pigmentary change and vitiligo is also substantial, especially in children with darker skin. The safety of DPCP in children <10 years is not established.,,
Anthralin 0.5% to 1% once daily to twice a week has been used topically, as short contact therapy in children with AA. It has shown a response rate of 42%. But, like other topical agents, it is also associated with a high relapse rate of over 50%., Significant hair regrowth may take 3 months of therapy and the peak effect was not obtained before 12 months of therapy. Italian expert committee on AA recommends the use of anthralin in children <3 years in preference to topical steroids for the treatment of limited AA in the chronic phase. Localized pigmentation may be a distressing side effect of anthralin application in dark-complexioned children.
Although, it is prescribed fairly commonly as an adjuvant therapy even in children with AA. But, there is not enough published literature on this subject. The concentration used in children varies from 1% to 5%. It is not advisable to use on larger surface areas, because of the potential of developing side effects.
Topical calcineurin inhibitors
Both pimecrolimus and tacrolimus have been used as a steroid-sparing agents in the treatment of children with AA. Tacrolimus 0.1.% ointment failed to produce satisfactory growth of hair in the study reported by Kuldeep et al., while others observed a variable response (40-100%) in children. Tacrolimus 0.1% ointment has been reported to be effective in 40-100% of the patient, and no side effects were reported in any of these children.
Majumdar et al. reported partial hair regrowth in 6 out of the 7 children of AA. They advised their patients to wrap a cotton towel soaked in highly diluted form of methoxy psoralen solution as a turban (Turban PUVAsol) around the head and expose the scalp to sunlight after half an hour for 2 hours.
| Systemic Agents|| |
Systemic steroids are recommended in acute AA with SALT score >50% and >30% in children aged 7–12 and 13–18, respectively, as per the guidelines issued by AA Consensus of Experts. They have been used as oral, intramuscular, and intravenous preparations in children with AA, and have been found to be effective in just over seventy percent of cases., The dosage commonly used varies from 0.5-2 mg/kg/day of prednisolone, or equivalent dose of any other preparation like betamethasone or dexamethasone. However, they are associated with very high relapse rate (63%). Corticosteroids, when given in weekly or monthly pulse form are associated with lesser side effects., Steroid therapy does not alter the longterm outcome of AA and is ineffective in ophiasis type of AA. Recent publications highlight the risk for avascular necrosis in children put on systemic steroids. The risk for developing fractures is increased in children who are on systemic steroids for more than 3 months. Prednisolone is preferrable to dexamethasone, as the growth suppressive potency of dexamethasone in children is 18 times more than that than prednisolone.
Methotrexate was well tolerated in children with severe AA and the efficacy was sustained over a prolonged period. A recently published meta-analysis concluded that the response to Methotrexate was lower in children with AA compared to adults. However, a significant hair growth was observed in 7 out of 10 children with severe recalcitrant AA who were on 5-20 mg of weekly methotrexate with a good steroid-sparing effect. Similarly, the response to methotrexate was satisfactory in 8 out of 14 children who took MTX for severe AA. There were no major adverse events. Best results were noticed in children <10 years of age. A target dose of 0.4 mg/kg/week is recommended by an international expert panel on AA for the effective management of severe pediatric AA. Maximal efficacy was obtained within 1 year of methotrexate use as a monotherapy in AA.
Cyclosporine has been used both as monotherapy and in combination with steroids. for management of AA in children and adults. However, the data pertaining to childhood AA could not be extracted for critical evaluation with regard to long-term safety and efficacy.
| JAK Inhibitors|| |
The only Food and Drug Administration approved dermatologic indication for this class of drugs is psoriatic arthritis. But tofacitinib (a JAK 3 and 1 inhibitor, used off-label in the management of AA and others such as (Ruxolitinib, Baricitinib), have been tested in clinical trials. Significant improvement with hair growth of at least 50 percent was seen in half of the adult patients who were put on tofacitinib for the treatment of AA. However, the improvement was not sustained upon discontinuation of the medication. Till date, the published data on the use of tofacitinib in childhood AA have been sparse with few case reports and small case series., They have used at a doses ranging from 2.5 mg to 10 mg/day. The clinical improvement may take 4 months in some patients. Common side effects include respiratory tract infections, diarrhea, transaminitis and mild drop in white blood cell counts. Serious adverse events are rare in patients receiving this medication for dermatological diseases.
| Topical JAK inhibitors|| |
Meanwhile, due to the concerns of potential long-term adverse effects of JAK inhibitors related to immune suppression, the researchers have been toying with the idea of using these agents topically, to offset systemic complications. Both, tofacitinib and ruxolitinib have been tried in topical formulations in different concentrations, and have shown to be efficacious even in pediatric AA.,, 4 out of 6 patients responded variably (range 20-95%) to 2% tofacitinib ointment or ruxolitinib cream in the study reported by Bayart et al.
| Conclusion|| |
Pediatric AA still remains a challenge for the treating physician because of the very limited treatment options available. Potent topical steroids are still the treatment of the first choice in children with patchy AA. Systemic steroids are effective in acute AA. Methotrexate is a safe and durable option for controlling severe AA. JAK inhibitors may play a significant role in the near future for the management of severe forms of pediatric AA (AT and AU). As of now, there are only limited data available in the literature, in children, and long-term safety and efficacy are yet to be determined.
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Conflicts of interest
There are no conflicts of interest.
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